Inhibition of Granulocyte-macrophage Colony Formation in Vitro by Substituted Isatin Thiosemicarbazones

The 1-methylisatin derivative of isatin thiosemicarbazone was previously shown to inhibit granulocyte-macrophage colony growth in vitro by an action at the early stages of colony development. The parent compound isatin thiosemicarbazone and 25 other derivatives were tested, and a wide range of activity was found (50% colony inhibition from 0.07 to > 100 mug per ml of culture). High activity was not associated with any specific substituent although 1-methyl or 1-ethyl isatin groups in association with 4'4' morpholino or 4'4' tetramethylene thiosemicarbazone substitutions were within the most active group. No correlation between the antimarrow and known antiviral activities of these compounds was apparent. Two of the more active compounds were compared with methisazone and were shown to have the same property of selective action on the early stages of granulocyte-macrophage differentiation in culture. It is suggested that this group of compounds might possibly provide some useful antileukemia agents.